A: To a quantity of Capsule contents,equivalent to about 2.5mg of oxycodone,add 5mLof a mixture of methanol and water (4:1),sonicate for 5minutes,and shake by mechanical means for 15minutes.Allow to settle,and use the clear supernatant as the test solution.Prepare a Standard solution of USP Oxycodone RSin the mixture of methanol and water (4:1)containing 0.5mg per mL,and a second Standard solution of USP Acetaminophen RSin the same solvent containing 0.5Jmg per mL,Jbeing the ratio of the labeled amount,in mg,of acetaminophen to the labeled amount,in mg,of oxycodone per Capsule.Apply separate 20-µLportions of the test solution and the Standard solutions to a thin-layer chromatographic plate (see Chromatography á621ñ)coated with a 0.25-mm layer of silica gel mixture.Allow the spots to dry,and develop the chromatogram in a solvent system consisting of a mixture of butyl alcohol,water,and glacial acetic acid (4:2:1)until the solvent front has moved about three-fourths of the length of the plate.Remove the plate from the developing chamber,mark the solvent front,and allow the plate to air-dry for about 30minutes.Expose the plate to iodine vapors in a closed chamber,and locate the spots:the RFvalues of the principal spots obtained from the test solution correspond to those obtained from the respective Standard solutions.

B: The retention times of the major peaks in the chromatogram of the Assay preparationcorrespond to those in the chromatogram of the Standard preparation,as obtained in the Assay.

Medium: 0.1Nhydrochloric acid;900mL.

Apparatus 2: 50rpm.

Time: 45minutes.

Procedure— Determine the amounts of oxycodone (C18H21NO4)and acetaminophen (C8H9NO2)dissolved,employing the procedure set forth in the Assay,making any necessary volumetric adjustments,including adjusting the solution under test to a pHof about 5.5before injecting.

Tolerances— Not less than 75%(Q)of the labeled amounts of C18H21NO4and C8H9NO2is dissolved in 45minutes.

Solvent mixture— Prepare a suitable mixture of 0.05Mdibasic potassium phosphate and methanol (9:1),and adjust with phosphoric acid to a pHof 4.0.Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).

Mobile phase— Add 950mg of monobasic potassium phosphate to 1000mLof water.Add 1mLof phosphoric acid,and stir until dissolved.While stirring,add 1mLof n-nonylamine,and stir until a clear solution is obtained.Adjust with potassium hydroxide TSto a pHof 4.9±0.1.Mix 9volumes of this solution with 1volume of methanol.Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).

Oxycodone standard stock solution— Dissolve an accurately weighed quantity of USP Oxycodone RSin Solvent mixtureto obtain a solution having a known concentration of about 0.075mg per mL.

Standard preparation— Transfer about 0.75Jmg of USP Acetaminophen RS,accurately weighed,Jbeing the ratio of the labeled amount,in mg,of acetaminophen to that of oxycodone equivalent,to a 25-mLvolumetric flask,add about 10mLof Solvent mixture,and mix to dissolve.Add 10.0mLof Oxycodone standard stock solution,dilute with Solvent mixtureto volume,and mix.Transfer 5.0mLof the solution so obtained to a 50-mLvolumetric flask,dilute with Mobile phaseto volume,and mix.This solution contains about 0.003mg of USP Oxycodone RSand 0.003Jmg of USP Acetaminophen RSper mL.

Assay preparation— Weigh the contents of not fewer than 20Capsules.Mix the contents,and transfer an accurately weighed portion of the powder,equivalent to about 4.5mg of oxycodone,to a suitable container.Add 150.0mLof Solvent mixture,and shake by mechanical means for 1hour.Transfer 5.0mLof the solution so obtained to a 50-mLvolumetric flask,dilute with Mobile phaseto volume,and mix.Pass the resulting solution through a membrane filter having a 0.5-µm or finer porosity,discarding the first 10mLof the filtrate.Use the filtrate.

Chromatographic system (see Chromatography á621ñ)— The liquid chromatograph is equipped with a 214-nm detector and a 4.6-mm ×25-cm column that contains 5-µm packing L1.The column is maintained at a temperature of 40.The flow rate is about 2mLper minute.Chromatograph the Standard preparation,and record the peak responses as directed for Procedure:the relative retention times are about 0.6for oxycodone and 1.0for acetaminophen;the resolution,R,between acetaminophen and oxycodone is not less than 2.4;and the relative standard deviation for replicate injections is not more than 2.0%.

Procedure— Separately inject equal volumes (about 20µL)of the Standard preparationand the Assay preparationinto the chromatograph,record the chromatograms,and measure the responses for the major peaks.Calculate the quantity,in mg,of oxycodone (C18N21NO4)in the portion of Capsules taken by the formula: in which Cis the concentration,in mg per mL,of USP Oxycodone RSin the Standard preparation;and rUand rSare the oxycodone peak responses obtained from the Assay preparationand the Standard preparation,respectively.Calculate the quantity,in mg,of acetaminophen (C8H9NO2)in the portion of Capsules taken by the formula: in which Cis the concentration,in mg per mL,of USP Acetaminophen RSin the Standard preparation;and rUand rSare the acetaminophen peak responses obtained from the Assay preparationand the Standard preparation,respectively.